Perianal fistulas are a common complication of Crohn’s disease and are estimated to affect up to 28% of Crohn’s patients during the first two decades after diagnosis [6, 7]. They severely impair patients’ quality of life and cause substantial morbidity [8]. At present, the only approved drug for this complication is the anti-TNF monoclonal antibody infliximab. However, approximately 70–80% of these fistulas are complex fistulas that are particularly refractory to conventional medical treatment.

Recently, stem cell therapies that have mainly used expanded mesenchymal stem cells (MSCs) have shown promising effects [9]. In a phase 3 randomized, double-blind controlled trial, Panés et al. showed that a significantly greater proportion of patients achieved combined remission at 24 weeks after treatment with allogeneic adipose-derived MSCs than with treatment with placebo [10]. The efficacy of local injections of increasing doses of allogeneic bone marrow-derived MSCs was shown by complete healing at 12 weeks in seven of fifteen patients who received MSCs, compared with two of six patients who received a placebo [11]. Only one case series has compared the use of ADSVF with the use of expanded MSCs. In that series, five patients received autologous MSCs derived from adipose tissue, and four patients received ADSVF cells. The results indicated that strategies based on cell expansion prior to implantation might be more effective than those involving the direct use of ADSVF isolated from a lipoaspirate sample [12].

From a regulatory point of view, the aforementioned therapies fall under the framework of directive 1394/2007 from the European Parliament and the European Council, which described a new category of health products referred to as “advanced therapy medicinal products” (ATMPs). As ATMP production must occur in accordance with pharmaceutical industry GMP, production costs have been significantly increased. Consequently, the use of ATMPs will barely be sustainable for public institutions.

In fact, 10 years after the publication of the above regulation, few of these therapies have received marketing authorization. However, although 2 to 3 weeks of expansion are needed to produce expanded MSCs, ADSVF cells can be manufactured within a few hours, allowing for lipoaspiration and reinjection to be performed on the same day. This point should be considered from a cost-effectiveness perspective.

This report provides the first description of a therapeutic strategy that combines the volumizing use of microfat and the trophic and regenerative effects of clinical-grade ADSVF in a 1-day procedure. Our results demonstrate this procedure’s feasibility, its good short-term tolerance profile, and its potential efficacy. In fact, we obtained promising effects with complete clinical and radiological healing of the fistula without any secondary effects. Although the mechanism of action of ADSVF remains poorly understood, findings from prior preclinical and clinical studies in various fields suggest that the combination of angiogenic and anti-inflammatory effects of ADSVF [13, 14] is primarily attributable to the high proportion of MSCs and endothelial progenitor cells; in the reported case, these two types of cells accounted for 38.6% and 4.3%, respectively, of the 22.8 million injected cells. The synergistic effects of these two cell subsets in tissue regeneration and neovascularization have previously been described [15]. As has been consistently reported in the literature, the immunomodulatory properties of ADSVF might be attributable to MSCs, which can reduce the production of pro-inflammatory cytokines and induce the regulatory T-cell phenotype [1618]. However, these properties have primarily been reported for allogeneic MSCs from healthy donors and should be discussed in the context of an autologous therapy for Crohn’s patients.